We are planning to study the effects of a nitric oxide-generating presursor, L-arginine, on the inflammatory response to intravenous endotoxin. Nitric oxide (NO) is a small molecular weight, highly reactive inorganic gas that has been shown in both animal and human studies to have multiple biologic functions, including neurotransmission, vasomotor control, immune modulation, and bronchodilatation, and as an effector molecule can destroy microorganisms. Its role in the pathophysiology of the sepsis syndrome has been suggested from both animal and human studies. In contrast to the evidence suggesting harmful effects of NO in sepsis, there are data that suggest that NO may have important beneficial and immunoregulatory effects during acute inflammation. To evaluate the effects of enhanced nitric oxide production on inflammatory responses to endotoxin in humans, we will administer an infusion of L-arginine. We postulate that by increasing substrate availability for nitric oxide production (L- arginine), beneficial effects of NO on cytokine production, leukocyte adhesion, and platelet aggregation will be observed. In order to study the effects of L-arginine in a manner that is relatively independent of the release of hormonal secretagogues (which occurs with doses of 30 grams/30 minutes), we will infuse 100 mg/kg/hr of L-arginine for a 6- hour study period (total dose infused approximately 42 grams/6 hours). The study will be performed in two phases. The initial phase will evaluate the effects of L-arginine infusion alone, and the second phase will evaluate the effects of L-arginine on endotoxin associated inflammation after intravenous endotoxin. The following parameters will be evaluated: exhaled NO, plasma and urine nitrates and nitrosothiols, plasma L-arginine levels, hormone, catecholamines, cell functional studies (expression of cell surface markers for adhesion molecules and cytokine receptors), platelet aggregation and markers of platelet degranulation, plasma for acute phase reactants, markers of endothelial cell monocyte, and neutrophil activation and serial echocardiograms.